Asymmetric Synthesis of (+)-allo-Quercitol and (+)-talo-Quercitol via Free Radical Cycloisomerization of an Enantiomerically Pure Alkyne-Tethered Aldehyde Derived from a Carbohydrate

• Published in: Journal of organic chemistry Vol. 66; no. 25; pp. 8370 - 8378
• Main Authors: YADAV, J. S., MAITI, Arup, SANKAR, A. Ravi, KUNWAR, A. C.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14-12-2001
• Subjects: Aldehydes - chemistry; Alkynes - chemistry; Carbohydrates - chemistry; Cyclization; Free Radicals - chemistry; Indicators and Reagents; Inositol - analogs & derivatives; Inositol - chemical synthesis; Magnetic Resonance Spectroscopy; Molecular Conformation; Spectrophotometry, Infrared; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo010455m

We describe for the first time the free radical cyclization of enantiomerically pure alkyne-tethered aldehydes obtained from a carbohydrate (6, 7). The synthesis of compounds 6 and 7 obtained from a derivative of D-ribose is reported. These radical precursors have been submitted to cyclization with tributyltin hydride plus azobisisobutyronitrile to yield, after ring closure, two carbocycles, respectively. These carbocycles have been obtained as mixtures of E and Z vinyltin isomers, but with excellent diastereoselection at the new stereocenter formed during the ring closure. After protodestannylation, only one diastereomer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established by detailed (1)H NMR analysis. The specific transformation of 7-methoxymethoxy-2,2-dimethyl-4-methylene-5-tert-butyldimethylsilyloxy-(3aR,5S,7S,7aS)-perhydrobenzo[d][1,3]dioxole into optically pure (+)-allo-quercitol and (+)-talo-quercitol is described. From these results, we conclude that under an appropriate choice of radical precursors and conditions, the synthesis of highly functionalized cyclohexane derivatives of biological interest is now available.